Fluorine-19 MR Molecular Imaging of Angiogenesis on Vx-2 Tumors in Rabbits Using α ν β 3-Targeted Nanoparticles

Jochen Keupp¹, Shelton D. Caruthers^2,3, Jrgen Rahmer¹, Todd A. Williams³, Samuel A. Wickline³, Gregory M. Lanza³

Anti-angiogenic therapy in combination with established chemotherapy or radiation therapy has entered clinical practice for lung, colon and breast cancer. However, effectiveness of anti-angiogenic pre-treatment is substantially varying among patients. Given the high cost and severe side effects, there is a strong clinical need for enhanced patient stratification, which could be based on MRI of angiogenesis using targeted imaging agents. ανβ3-integrin targeted nanoparticle (NP) emulsions, labeled with R1-enhancing Gd-chelates, were previously shown to allow three-dimensional MR mapping of tumor angiogenesis in small animals. These studies were based on δR1 mapping from two image sets taken before and after NP injection. The present study shows, that the perfluorocarbon (PFC) core of the same targeted NP can be used as a ¹⁹F MR label to map angiogenesis around Vx-2 tumors (adenocarcinoma) in rabbits. With simultaneous ¹⁹F and ¹H MR, diagnostic imaging is only required at a single time point post-injection injection and may offer the ability of direct absolute quantification.